This is a randomized, multi-site, adaptive, open-label clinical trial comparing the immune response to different additional doses of COVID-19 vaccine in participants with autoimmune disease requiring IS medications. All study participants will have negative serologic or suboptimal responses (defined as a Roche Elecsys® Anti-SARS-CoV-2 S result ≤200 U/mL) or a low immune response (defined as a Roche Elecsys® Anti-SARS-CoV-2 S result \>200 U/ml and ≤2500 U/mL) to their previous doses of COVID-19 vaccine. The study will focus on 5 autoimmune diseases in adults: * Systemic Lupus Erythematosus (SLE) * Rheumatoid Arthritis (RA) * Multiple Sclerosis (MS) * Systemic Sclerosis (SSc), and * Pemphigus. This study will focus on 4 autoimmune diseases in pediatric participants: * Systemic Lupus Erythematosus (SLE) * Juvenile Idiopathic Arthritis (JIA) * Pediatric-Onset Multiple Sclerosis (POMS) * Juvenile Dermatomyositis (JDM)
Adult Population: Stage 1 of this trial will enroll up to a maximum of 900 adult study participants (up to 60 participants per arm). Participants will be assigned to one of 3 cohorts based on their IS regimens: * Cohort A: Receipt of MMF or MPA * Cohort B: Receipt of MTX * Cohort C: Receipt of any BCDT within the past 18 months. Treatment Arms: Participants in Cohorts A, B, and C will be assigned to receive an additional dose of the same COVID-19 vaccine as their original vaccine series. The trial initially enrolled participants who were vaccinated with the Pfizer-BioNTech COVID-19 Vaccine, the Moderna COVID-19 Vaccine, and the Janssen COVID-19 Vaccine. Update: Arms to receive an additional homologous vaccine dose after an initial Janssen COVID 19 Vaccine were closed to enrollment after the CDC updated its recommendations to express a clinical preference for individuals to receive an mRNA COVID-19 vaccine over the Janssen COVID-19 vaccine. All Adult Stage 1 treatment arms were closed to enrollment on 15 August 2022. Participants in Cohorts A and B will be randomized into 2 IS medication treatment plans as follows: * Participants continue to take their cohort-defining IS medications without alterations in schedule and dosing. * Participants withhold their cohort-defining IS medications before and after the additional homologous vaccine dose per protocol instructions. A participant will be enrolled in the study for a maximum of approximately 13 months. Stage 2 of this trial will include up to a maximum of 960 adult study participants (up to 80per arm) with a Roche Elecsys® Anti-SARS-CoV-2 S result ≤2500 U/mL after previous COVID-19 vaccine administration (at least 3 doses of mRNA vaccine(s) or 2 doses of the Janssen COVID-19 Vaccine). Participants will be eligible to receive a dose of an alternative COVID-19 vaccine. Participants may have received their previous COVID-19 vaccine prior to enrollment in the study ("newly recruited participant"), or they may have received their previous COVID-19 vaccine as a study participant and then (re-) enter into Stage 2 ("rollover participant"). Participants can also roll over into Stage 2 via two pathways: * Stage 1 participant rolls over to Stage 2 * Stage 2 participant rolls over to a different Stage 2 treatment arm Participants will be allocated to 1 of 3 cohorts based on their IS regimens: * Cohort D: Receipt of MMF or MPA * Cohort E: Receipt of MTX * Cohort F: Receipt of any BCDT within the past 18 months. Treatment Arms: Participants in Cohorts D, E, and F will receive a dose of an alternative COVID-19 vaccine compared to their previous COVID-19 vaccine doses. Originally, participants who previously received 3 total doses of a single mRNA vaccine (Moderna COVID-19 Vaccine OR Pfizer- BioNTech COVID-19 Vaccine) received their choice of either the Janssen vector-based COVID-19 vaccine or the other mRNA COVID-19 vaccine, and participants who previously received 2 doses of the Janssen vector based COVID-19 vaccine received the Moderna COVID-19 Vaccine. Update: Beginning with v4.0 of the protocol, this trial will not utilize the Janssen vector-based COVID-19 vaccine. Participants who previously received 3 total doses of a single mRNA vaccine will receive their choice of an alternative mRNA COVID-19 vaccine or the Sanofi-GSK protein based COVID-19 vaccine. Participants who previously received 4 or more doses of a single mRNA vaccine or 3 or more doses of a mixture mRNA vaccines (Moderna COVID-19 Vaccine AND Pfizer-BioNTech COVID-19 Vaccine, in any order or combination) will receive the Sanofi-GSK protein-based COVID-19 vaccine. Participants in Cohorts D and E will withhold their cohort-defining IS medications before and after the alternative vaccine dose per protocol instructions. Participants in Cohort F who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications before and after the alternative vaccine dose per protocol instructions. Visits to assess endpoints will occur at Baseline (Week 0), Week 4 ± 1 week, Week 12 ± 2 weeks, Week 24 ± 2 weeks, Week 36 ± 2 weeks, and Week 48 ± 2 weeks. A participant who is newly recruited to the study for entry into Stage 2 may be on study for up to a maximum of 13 months. A participant who enters Stage 2 after a serologic negative, suboptimal, or low immune response to their Stage 1 vaccine dose may be on study for up to a maximum of 26 months. Rollover participants will discontinue follow-up as part of Stage 1 upon rollover into Stage 2. A participant who rolls over to a different Stage 2 treatment arm 2 after a serologic negative, suboptimal, or low immune response to another Stage 2 vaccine dose may be on study for up to a maximum of 38 months. Pediatric Population: Stage 1 in the pediatric portion of this trial will enroll up to a maximum of 800 participants (2-17 years of age) with a Roche Elecsys® Anti-SARS-CoV-2 S result ≤2500 U/mL after receiving an initial COVID-19 vaccine regimen (up to 80participants per arm). Vaccines will be included in this protocol as they receive EUA or approval by FDA for a given age group. Pediatric participants will have 1 of 4 autoimmune diseases: pediatric SLE, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), or pediatriconset multiple sclerosis (POMS). Participants will be assigned to 1 of 3 cohorts based on their IS regimens: * Cohort A: Receipt of MMF or MPA * Cohort B: Receipt of MTX * Cohort C: Receipt of any BCDT within the past 18 months. Treatment Arms: Participants in Cohorts A, B, and C will be assigned to receive an additional dose of the same vaccine as their original vaccine series. Based on FDA EUA status, pediatric participants were initially eligible to receive the Pfizer-BioNTech COVID-19 Vaccine only. Participants in Cohorts A and B will be randomized into 2 IS medication treatment plans as follows): * Participants continue to take their cohort-defining IS medications without alterations in schedule and dosing. * Participants withhold their cohort-defining IS medications before and after the additional homologous vaccine dose per protocol instructions. A participant will be enrolled in the study for a maximum of approximately 13 months. Stage 2 of the pediatric portion of this trial will include up to a maximum of 480 pediatric study participants (up to 80 per arm) with a Roche Elecsys® Anti-SARS-CoV-2 S result ≤2500 U/mL after previous COVID-19 vaccine administration (an age-appropriate EUA-authorized or FDA-approved initial COVID-19 vaccine regimen plus 1 additional dose of the same vaccine). All participants (2-17 years of age) who previously received doses of the Pfizer-BioNTech COVID-19 Vaccine are eligible to receive an age-appropriate dose of the Moderna COVID-19 Vaccine. Participants 12 through 17 years of age who previously received doses of the Moderna COVID-19 vaccine are eligible to receive an age-appropriate dose of the Pfizer-BioNTech COVID-19 Vaccine. Participants will be eligible to receive a dose of an alternative COVID-19 vaccine. Participants may have received their previous COVID-19 vaccine as a study participant and then enter into Stage 2 ("rollover participant"), or they may have received their previous COVID-19 vaccine prior to enrollment in the study ("newly recruited participant"). Participants will be allocated to 1 of 3 cohorts based on their IS regimens: * Cohort D: Receipt of MMF or MPA (± other rheumatic disease medications, including biologics) o Participants who are taking MMF or MPA (without additional B cell depleting medications or MTX) will be placed in this cohort. * Cohort E: Receipt of MTX (± other rheumatic disease medications, including biologics) o Participants who are taking MTX (without additional B cell depleting medications or MMF/ MPA) will be placed in this cohort. * Cohort F: Receipt of B cell depletion therapy within the past 18 months (± other rheumatic disease medications) o Participants taking B cell depletion medications, regardless of whether they are also taking MMF or MTX, will be placed in this cohort. Treatment Arms: Participants in Cohorts D, E, and F will receive a dose of an alternative COVID-19 vaccine compared to their previous COVID-19 vaccine doses. Participants who previously received age-appropriate doses of a single mRNA vaccine (Moderna COVID-19 Vaccine OR Pfizer-BioNTech COVID-19 Vaccine, as noted above) will receive the other mRNA COVID-19 vaccine. Beginning with v7.0 of the protocol all vaccines used are bivalent versions replacing original monovalent versions. Participants in Cohorts D and E will withhold their cohort-defining IS medications before and after the alternative vaccine dose per protocol instructions (see Section 7.1.1 Protocol-mandated Medications). Participants in Cohort F who are taking MMF, MPA, or MTX in addition to B cell depletion therapies (BCDTs) will withhold these medications before and after the alternative vaccine dose per protocol instruction. A participant who enters Stage 2 after a serologic negative, suboptimal, or low immune response to their Stage 1 vaccine dose may be on study for up to a maximum of 26 months. Rollover participants will discontinue follow-up as part of Stage 1 upon rollover into Stage 2. A participant who is newly recruited to the study for entry into Stage 2 may be on study for up to a maximum of 13 months. Adaptive Design An adaptive design will be employed such that cohorts and arms defined by additional vaccine doses and IS treatment plans may be added or modified based on emerging data from existing and new FDA Emergency Use Authorization (EUA) or approvals of COVID-19 vaccines: * New cohorts may be defined based on changes in the medication groups if it becomes obvious that certain medications are highly associated with suboptimal or low immune serologic response to initial COVID-19 vaccine regimen. * Cohorts may limit or expand the autoimmune diseases that are eligible to be included in the clinical trial and may include expansion cohorts of underrepresented diseases. * New cohorts may include participants whose antibody response falls to suboptimal or low immune levels over time. * Based upon timing of the FDA EUA authorization for children of each of the COVID-19 vaccines used in this trial, the age range of the inclusion criteria may be expanded. * Allocation or randomization to treatment with new COVID-19 vaccines may be incorporated into the design when the products become available. * Identification of additional strategies to enhance vaccine responsiveness in autoimmune diseases, including a temporary switch of immunomodulatory medications.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
258
Administration: One dose administered intramuscularly.
Administration: One dose administered intramuscularly.
Administration: One dose administered intramuscularly.
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Participants continue to take their immunosuppressive (IS) medications for management of their autoimmune disease without alterations in schedule and dosing.
Participants will continue to take their prescribed immunosuppressive (IS) medications without alterations in schedule and dosing.
One dose administered intramuscularly
Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions.
Participants withhold their cohort-defining immunosuppressive (IS) medications for management of their autoimmune disease before and after the additional vaccine dose per protocol instructions.
Participants who are taking MMF, MPA, or MTX in addition to BCDTs will withhold these medications (MMF, MPA, or MTX ) before and after the additional vaccine dose per protocol instructions. Participants will continue to take their prescribed BCDTs without alterations in schedule and dosing.
Administration: One dose administered intramuscularly.
Administration: One dose administered intramuscularly.
UCLA Medical Center: Division of Rheumatology
Los Angeles, California, United States
Yale University School of Medicine: Rheumatology, Allergy & Immunology
New Haven, Connecticut, United States
The Emory Clinic: Division of Rheumatology
Atlanta, Georgia, United States
Indiana University Medical Center, Riley Hospital for Children
Indianapolis, Indiana, United States
Massachusetts General Hospital: Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases
Boston, Massachusetts, United States
Percent of Stage 1 Adult Participants Who Have a Protective Antibody Response at Week 4
Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center (NIAID-VRC) Meso Scale Discovery (MSD) 3 plex assay (Wu-1 full-length spike, receptor binding domain (RBD), and N proteins). A threshold for achieving a protective antibody response was not established for the NIAID VRC MSD assay. The intent was to use a pre-established threshold to define a protective antibody response. However, correlates from previous studies could not be extrapolated to the CoV-2 variants circulating over the entire course of this trial.
Time frame: Week 4 Status Post Receipt of COVID-19 Vaccination
Percent of Stage 2 Adult Participants Who Have a Protective Antibody Response at Week 4
Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center (NIAID-VRC) Meso Scale Discovery (MSD) 3 plex assay (Wu-1 full-length spike, receptor binding domain (RBD), and N proteins). A threshold for achieving a protective antibody response was not established for the NIAID VRC MSD assay. The intent was to use a pre-established threshold to define a protective antibody response. However, correlates from previous studies could not be extrapolated to the CoV-2 variants circulating over the entire course of this trial.
Time frame: Week 4 Status Post Receipt of COVID-19 Vaccination
Percent of Stage 2 Pediatric Participants Who Have a Protective Antibody Response at Week 4
Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center (NIAID-VRC) Meso Scale Discovery (MSD) 3 plex assay (Wu-1 full-length spike, receptor binding domain (RBD), and N proteins). A threshold for achieving a protective antibody response was not established for the NIAID VRC MSD assay. The intent was to use a pre-established threshold to define a protective antibody response. However, correlates from previous studies could not be extrapolated to the CoV-2 variants circulating over the entire course of this trial.
Time frame: Week 4 Status Post Receipt of COVID-19 Vaccination
Percentage of Stage 1 Adult Participants Who Seroconverted
Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center Meso Scale Discovery 3 plex assay. For concentrations below the lower limit of detection (LLOD), numeric values equivalent to LLOD/2 were assigned; concentrations above the upper limit of quantification were reported without adjustments. Antibody results collected after a documented COVID-19 infection, monoclonal antibody use, or COVID-19 vaccine given off-study were excluded from the analyses. Participants missing antibody data were considered missing-completely-at-random. Seroconversion was assessed in the subgroup of participants who were anti-COVID-19 antibody negative at Week 0; defined as a result less than or equal to the positive threshold value (spike=10.8424, RBD=14.0858). Anti-COVID-19 antibody negative at Week 0 is defined separately for spike and RBD. Seroconversion was defined as having a result greater than the positive threshold at the Week 4 visit.
Time frame: Week 4 Status Post Receipt of COVID-19 Vaccination
Percentage of Stage 2 Adult Participants Who Seroconverted
Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center Meso Scale Discovery 3 plex assay. For concentrations below the lower limit of detection (LLOD), numeric values equivalent to LLOD/2 were assigned; concentrations above the upper limit of quantification were reported without adjustments. Antibody results collected after a documented COVID-19 infection, monoclonal antibody use, or COVID-19 vaccine given off-study were excluded from the analyses. Participants missing antibody data were considered missing-completely-at-random. Seroconversion was assessed in the subgroup of participants who were anti-COVID-19 antibody negative at Week 0; defined as a result less than or equal to the positive threshold value (spike=10.8424, RBD=14.0858). Anti-COVID-19 antibody negative at Week 0 is defined separately for spike and RBD. Seroconversion was defined as having a result greater than the positive threshold at the Week 4 visit.
Time frame: Week 4 Status Post Receipt of COVID-19 Vaccination
Fold Increase in Stage 1 Adult Anti-COVID-19 Antibody Levels
Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center Meso Scale Discovery 3 plex assay. For concentrations below the lower limit of detection (LLOD), numeric values equivalent to LLOD/2 were assigned; concentrations above the upper limit of quantification were reported without adjustments. Antibody results collected after a documented COVID-19 infection, monoclonal antibody use, or a COVID-19 vaccine given off-study were excluded from the analyses. Participants with missing antibody data were considered missing-completely-at-random. Fold increase was assessed in the subgroup of participants who were anti-COVID-19 antibody positive at Week 0; defined as having a result greater than the positive threshold value (spike=10.8424, RBD=14.0858). Anti-COVID-19 antibody positive at Week 0 is defined separately for spike and RBD. Fold increase = (antibody response at Week 4)/(antibody response at Week 0).
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Boston Children's Hospital: Department of Pediatrics, Rheumatology Program
Boston, Massachusetts, United States
Brigham & Women's Hospital: Department of Medicine, Rheumatology, Immunology
Boston, Massachusetts, United States
University of Michigan Health System: Department of Internal Medicine, Division of Rheumatology
Ann Arbor, Michigan, United States
Washington University School of Medicine in St. Louis: Division of Rheumatology
St Louis, Missouri, United States
Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases
Manhasset, New York, United States
...and 19 more locations
Time frame: Week 4 Status Post Receipt of COVID-19 Vaccination
Fold Increase in Stage 2 Adult Anti-COVID-19 Antibody Levels
Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center Meso Scale Discovery 3 plex assay. For concentrations below the lower limit of detection (LLOD), numeric values equivalent to LLOD/2 were assigned; concentrations above the upper limit of quantification were reported without adjustments. Antibody results collected after a documented COVID-19 infection, monoclonal antibody use, or a COVID-19 vaccine given off-study were excluded from the analyses. Participants with missing antibody data were considered missing-completely-at-random. Fold increase was assessed in the subgroup of participants who were anti-COVID-19 antibody positive at Week 0; defined as having a result greater than the positive threshold value (spike=10.8424, RBD=14.0858). Anti-COVID-19 antibody positive at Week 0 is defined separately for spike and RBD. Fold increase = (antibody response at Week 4)/(antibody response at Week 0).
Time frame: Week 4 Status Post Receipt of COVID-19 Vaccination
Change in Stage 1 Adult Anti-COVID-19 Antibody Response
Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center (NIAID-VRC) Meso Scale Discovery (MSD) 3 plex assay (Wu-1 full-length spike, receptor binding domain (RBD), and N proteins). Wu-1 full-length spike and RBD were used to assess vaccine response. For concentrations below the lower limit of detection (LLOD), numeric values equivalent to LLOD/2 were assigned; concentrations above the upper limit of quantification were reported without adjustments. Antibody results collected after a documented COVID-19 infection, monoclonal antibody use, or a COVID-19 vaccine given off-study were excluded from the analyses. Participants with missing anti-COVID-19 antibody response data were considered to be missing-completely-at-random.
Time frame: Week 0 and Weeks 4 and 12 Status Post Receipt of COVID-19 Vaccination
Change in Stage 2 Adult Anti-COVID-19 Antibody Response
Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center (NIAID-VRC) Meso Scale Discovery (MSD) 3 plex assay (Wu-1 full-length spike, receptor binding domain (RBD), and N proteins). Wu-1 full-length spike and RBD were used to assess vaccine response. For concentrations below the lower limit of detection (LLOD), numeric values equivalent to LLOD/2 were assigned; concentrations above the upper limit of quantification were reported without adjustments. Antibody results collected after a documented COVID-19 infection, monoclonal antibody use, or a COVID-19 vaccine given off-study were excluded from the analyses. Participants with missing anti-COVID-19 antibody response data were considered to be missing-completely-at-random.
Time frame: Week 0 and Weeks 4 and 12 Status Post Receipt of COVID-19 Vaccination
Fold Inhibition of ACE2 Binding to SARS-CoV-2 Variant Antigens by Stage 1 Adult Samples
Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center (NIAID-VRC) Meso Scale Discovery (MSD) V-Plex ACE2 neutralization assay which measure antibodies that block the binding of angiotensin-converting enzyme 2 (ACE2) to the SARS-CoV-2 Spike antigens, including variants of the SARS-CoV-2 virus according to the manufacturer's instruction (MSD Catalog # K15654U). Antibody results collected after a documented COVID-19 infection, monoclonal antibody use, or a COVID-19 vaccine given off-study were excluded from the analyses. Participants with missing anti-COVID-19 antibody response data were considered to be missing-completely-at-random. Results are reported as fold inhibition by a sample relative to signal from a 'diluent only' control (maximum ACE2 binding to antigen). Highly neutralizing samples show high fold inhibition whereas negative or low samples show low fold inhibition of ACE2 binding.
Time frame: Week 0 and Weeks 4 and 12 Status Post Receipt of COVID-19 Vaccination
Fold Inhibition of ACE2 Binding to SARS-CoV-2 Variant Antigens by Stage 2 Adult Samples
Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center (NIAID-VRC) Meso Scale Discovery (MSD) V-Plex ACE2 neutralization assay which measure antibodies that block the binding of angiotensin-converting enzyme 2 (ACE2) to the SARS-CoV-2 Spike antigens, including variants of the SARS-CoV-2 virus according to the manufacturer's instruction (MSD Catalog # K15654U). Antibody results collected after a documented COVID-19 infection, monoclonal antibody use, or a COVID-19 vaccine given off-study were excluded from the analyses. Participants with missing anti-COVID-19 antibody response data were considered to be missing-completely-at-random. Results are reported as fold inhibition by a sample relative to signal from a 'diluent only' control (maximum ACE2 binding to antigen). Highly neutralizing samples show high fold inhibition whereas negative or low samples show low fold inhibition of ACE2 binding.
Time frame: Week 0 and Weeks 4 and 12 Status Post Receipt of COVID-19 Vaccination
Change in Stage 1 Adult Disease Activity as Measured by the Clinical Global Impression of Change (CGI-C)
The Clinical Global Impression of Change (CGI-C) is the clinician's global impression of a participant's clinical condition in terms of change relative to the start of treatment. Change is rated on a 7-point scale from 1 (very much improved) to 7 (very much worse). Higher score = more affected.
Time frame: Weeks 4 Status Post Receipt of COVID-19 Vaccine Dose
Change in Stage 2 Adult Disease Activity After Receipt of Additional Doses of COVID-19 Vaccine as Measured by the Clinical Global Impression of Change (CGI-C)
The Clinical Global Impression of Change (CGI-C) is the clinician's global impression of a participant's clinical condition in terms of change relative to the start of treatment. Change is rated on a 7-point scale from 1 (very much improved) to 7 (very much worse). Higher score = more affected.
Time frame: Weeks 4 Status Post Receipt of COVID-19 Vaccine Dose
Change in Adult Stage 1 Disease Activity as Measured by the Physician's Global Assessment
The Physician's Global Assessment of the participant's current disease activity is assessed on a 10 cm linear horizontal visual analog scale, where the left hand extreme of the line is considered "Very Good" (0 cm, no disease activity) and the right hand extreme is considered "Very Bad" (10 cm, severe disease activity).
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Adult Stage 2 Disease Activity After Receipt of Additional Doses of COVID-19 Vaccine as Measured by the Physician's Global Assessment
The Physician's Global Assessment of the participant's current disease activity is assessed on a 10 cm linear horizontal visual analog scale, where the left hand extreme of the line is considered "Very Good" (0 cm, no disease activity) and the right hand extreme is considered "Very Bad" (10 cm, severe disease activity).
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Disease Activity in Stage 1 Adult Participants With Systemic Lupus Erythematosus (SLE) as Measured by Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI)
The Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) is a validated, physician-based assessment tool used to measure the extent of lupus disease activity within the past 28 days. hSLEDAI total score is a weighted sum of the presence of 24 lupus disease symptoms and ranges from 0 to 105, with higher scores indicating more lupus disease activity present.
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Disease Activity in Stage 2 Adult Participants With Systemic Lupus Erythematosus (SLE) as Measured by Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI)
The Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) is a validated, physician-based assessment tool used to measure the extent of lupus disease activity within the past 28 days. hSLEDAI total score is a weighted sum of the presence of 24 lupus disease symptoms and ranges from 0 to 105, with higher scores indicating more lupus disease activity present.
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Disease Activity in Stage 1 Adult Participants With Systemic Lupus Erythematosus (SLE) as Measured by the Thanou Modified SELENA-SLEDAI Flare Index
The Thanou Modified Safety of Estrogens in Lupus Erythematosus: National Assessment- Hybrid Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) assesses systemic lupus erythematosus (SLE) disease activity and categorizes mild/moderate or severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), other disease activity criteria, and hospitalization due to SLE. The hSLEDAI is a validated, physician-based assessment tool used to measure the extent of lupus disease activity within the past 28 days. hSLEDAI total score is a weighted sum of the presence of 24 lupus disease symptoms and ranges from 0 to 105, with higher scores indicating more lupus disease activity present.
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Disease Activity in Stage 2 Adult Participants With Systemic Lupus Erythematosus (SLE) as Measured by the Thanou Modified SELENA-SLEDAI Flare Index
The Thanou Modified Safety of Estrogens in Lupus Erythematosus: National Assessment- Hybrid Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) assesses systemic lupus erythematosus (SLE) disease activity and categorizes mild/moderate or severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), other disease activity criteria, and hospitalization due to SLE. The hSLEDAI is a validated, physician-based assessment tool used to measure the extent of lupus disease activity within the past 28 days. hSLEDAI total score is a weighted sum of the presence of 24 lupus disease symptoms and ranges from 0 to 105, with higher scores indicating more lupus disease activity present.
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Disease Activity in Stage 1 Adult Participants With Rheumatoid Arthritis (RA) as Measured by Disease Activity Score 28 C-reactive Protein (DAS28-CRP)
The Disease Activity Score 28 C-reactive Protein (DAS28-CRP) is: a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (\>5.1=high disease activity; \<=3.2=low disease activity; \<2.6=remission); a continuous variable which is a composite of 4 variables(the number of tender joints out of 28, the number of swollen joints out of 28 joints, serum C-reactive protein in mg/L (CRP) and subject assessment of disease activity measure on a visual analogue scale (VAS) of 100 mm). Reference: van Gestel AM et al. Arthritis Rheum.1998; 41(10): 1845-50.
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Disease Activity in Stage 2 Adult Participants With Rheumatoid Arthritis (RA) as Measured by Disease Activity Score 28 C-reactive Protein (DAS28-CRP)
The Disease Activity Score 28 C-reactive Protein (DAS28-CRP) is: a score on a scale (0 to 10) indicating current activity of rheumatoid arthritis (\>5.1=high disease activity; \<=3.2=low disease activity; \<2.6=remission); a continuous variable which is a composite of 4 variables(the number of tender joints out of 28, the number of swollen joints out of 28 joints, serum C-reactive protein in mg/L (CRP) and subject assessment of disease activity measure on a visual analogue scale (VAS) of 100 mm). Reference: van Gestel AM et al. Arthritis Rheum.1998; 41(10): 1845-50.
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Disease Activity in Stage 1 Adult Participants With Systemic Sclerosis (SSc) as Measured by Disease Flare Activity
Severe disease flare included onset of new or significant worsening of internal organ involvement requiring hospitalization or change in treatment. Internal organ involvement included scleroderma renal crisis, interstitial lung disease, left or right sided heart failure, pulmonary arterial hypertension on right-sided heart catheterization or other worsening of internal organs.
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Disease Activity in Stage 2 Adult Participants With Systemic Sclerosis (SSc) as Measured by Disease Flare Activity
Severe disease flare included onset of new or significant worsening of internal organ involvement requiring hospitalization or change in treatment. Internal organ involvement included scleroderma renal crisis, interstitial lung disease, left or right sided heart failure, pulmonary arterial hypertension on right-sided heart catheterization or other worsening of internal organs.
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Disease Activity in Stage 1 Adult Participants With Pemphigus as Measured by Disease Area Index (PDAI) for Pemphigus
The Pemphigus Disease Area Index (PDAI) was developed by the International Pemphigus Committee and measures both activity of and damage due to pemphigus on the skin, scalp, and mucous membranes. Total scores can range from 0 to a possible 263 maximum score, with 250 points representing disease activity (120 points for skin activity, 10 points for scalp activity, and 120 points for mucosal activity) and 13 points representing disease damage. Higher scores reflect worse disease.
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Disease Activity in Stage 2 Adult Participants With Pemphigus as Measured by Disease Area Index (PDAI) for Pemphigus
The Pemphigus Disease Area Index (PDAI) was developed by the International Pemphigus Committee and measures both activity of and damage due to pemphigus on the skin, scalp, and mucous membranes. Total scores can range from 0 to a possible 263 maximum score, with 250 points representing disease activity (120 points for skin activity, 10 points for scalp activity, and 120 points for mucosal activity) and 13 points representing disease damage. Higher scores reflect worse disease.
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Disease Activity in Stage 1 Adult Participants With Multiple Sclerosis (MS) as Measured by Physician Assessed Relapse for MS
Relapse required: either criteria (a) with investigator determination of relapse or criteria (a) and (b): (a) New, recurrent or worsening neurological symptoms attributable to MS, that meet all of the following: i. Appeared or evolved subacutely (over \<3 months). ii. Persisting \>24 hours. iii. Can't be attributed to confounding factors. iv. Occur ≥30 days after onset of a prior confirmed relapse. (b) New, recurrent or worsening neurological symptoms accompanied by corresponding objective worsening on neurologic examination with an increase of any one of the following compared to the immediate prior assessment: i. ≥0.5 step(s) on the Expanded Disability Status Scale (EDSS), ii. ≥2 points on one Functional Systems Score (FSS), iii. ≥1 point on two or more FSS. Episodic spasms, sexual dysfunction, fatigue, mood change, or bladder/bowel urgency or incontinence will not suffice to establish relapse. Sexual dysfunction and fatigue will not contribute to the EDSS/FSS for assessing relapse.
Time frame: Screening and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Disease Activity in Stage 2 Adult Participants With Multiple Sclerosis (MS) as Measured by Physician Assessed Relapse for MS
Relapse required: either criteria (a) with investigator determination of relapse or criteria (a) and (b): (a) New, recurrent or worsening neurological symptoms attributable to MS, that meet all of the following: i. Appeared or evolved subacutely (over \<3 months). ii. Persisting \>24 hours. iii. Can't be attributed to confounding factors. iv. Occur ≥30 days after onset of a prior confirmed relapse. (b) New, recurrent or worsening neurological symptoms accompanied by corresponding objective worsening on neurologic examination with an increase of any one of the following compared to the immediate prior assessment: i. ≥0.5 step(s) on the Expanded Disability Status Scale (EDSS), ii. ≥2 points on one Functional Systems Score (FSS), iii. ≥1 point on two or more FSS. Episodic spasms, sexual dysfunction, fatigue, mood change, or bladder/bowel urgency or incontinence will not suffice to establish relapse. Sexual dysfunction and fatigue will not contribute to the EDSS/FSS for assessing relapse.
Time frame: Screening and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Disease Activity in Stage 2 Pediatric Participants With Juvenile Idiopathic Arthritis (JIA) as Measured by the Juvenile Arthritis Disease Activity Score 10 (JADAS10)
The Juvenile Arthritis Disease Activity Score 10-C-reactive Protein (JADAS10-CRP) is a score on a scale (0 to 40) indicating activity of juvenile idiopathic arthritis. Total active joints are scored 0 to 10, with an active joint count \>10 scored as 10 points. The Physician's Global Assessment and Patient's Global Assessment are measured on a 0-10 scale (0 cm, no disease activity to 10 cm, worst disease activity). CRP is normalized to a 0 to 10 scale according to the following formula: (CRP (mg/L) - 10)/10. CRP values \<10 mg/L are scored as 0, and CRP \>110 mg/L are scored as 10. The final score is given by the simple sum of its component. Higher scores indicate worse disease activity.
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Adult Stage 1 Disease Activity as Measured by the Patient-Reported Outcomes Measurement Information System (PROMIS-29)
The Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Short Form (Version 2.0) will be used to assess trends over time in this state of health measure. The PROMIS-29 consists of 7 domains related to physical, mental and social health. Raw scores are calculated for each domain and translated into a T-score per the PROMIS-29 scoring guide. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. Physical Function domain score is presented. A higher score represents better functioning for the Physical Function domain.
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Adult Stage 2 Disease Activity as Measured by the Patient-Reported Outcomes Measurement Information System (PROMIS-29)
The Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Short Form (Version 2.0) will be used to assess trends over time in this state of health measure. The PROMIS-29 consists of 7 domains related to physical, mental and social health. Raw scores are calculated for each domain and translated into a T-score per the PROMIS-29 scoring guide. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. Physical Function domain score is presented. A higher score represents better functioning for the Physical Function domain.
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Adult Stage 1 Disease Activity as Measured by the Patient Global Assessment
The Patient Global Assessment of the participant's current disease activity is assessed on a 10 cm linear horizontal visual analog scale, where the left hand extreme of the line is considered "Very Good" (0 cm, no disease activity) and the right hand extreme is considered "Very Bad" (10 cm, severe disease activity).
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Adult Stage 2 Disease Activity as Measured by the Patient Global Assessment
The Patient Global Assessment of the participant's current disease activity is assessed on a 10 cm linear horizontal visual analog scale, where the left hand extreme of the line is considered "Very Good" (0 cm, no disease activity) and the right hand extreme is considered "Very Bad" (10 cm, severe disease activity).
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Stage 1 Adult Disease Activity as Measured by the Patient Global Impression of Change (PGI-C)
The Patient Global Impression of Change (PGI-C) is the participant's global impression of their clinical condition in terms of change relative to the start of treatment. Change is rated on a 7-point scale from 1 (very much improved) to 7 (very much worse). Higher score = more affected.
Time frame: Weeks 4 Status Post Receipt of COVID-19 Vaccine Dose
Change in Stage 2 Adult Disease Activity as Measured by the Patient Global Impression of Change (PGI-C)
The Patient Global Impression of Change (PGI-C) is the participant's global impression of their clinical condition in terms of change relative to the start of treatment. Change is rated on a 7-point scale from 1 (very much improved) to 7 (very much worse). Higher score = more affected.
Time frame: Weeks 4 Status Post Receipt of COVID-19 Vaccine Dose
Percent of Stage 1 Adult Participants Who Experience Any Grade 1 or Higher Adverse Events Related to Study Vaccine
All unsolicited adverse events (AEs) (all grades) were collected from Day 1 through Day 28; solicited AEs were collected if they were ongoing at Day 7 (post vaccination); any flares of a secondary autoimmune disease, serious AEs, medically attended AEs, new onset chronic medical conditions, and COVID-19 infections were collected from Day 1 through the end of the participant's study participation. All AEs were classified by system organ class (SOC) and preferred term, according to a standardized thesaurus (Medical Dictionary for Regulatory Activities \[MedDRA\] version 24.0. Related AEs were defined as "possibly related" (the AE has a reasonable possibility to be related; there is evidence to suggest a causal relationship) or "related" (the adverse event is clearly related). Severity was assessed according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) 5.0.
Time frame: Up to Week 48 post study vaccination
Percent of Stage 2 Adult Participants Who Experience Any Grade 1 or Higher Adverse Events Related to Study Vaccine
All unsolicited adverse events (AEs) (all grades) were collected from Day 1 through Day 28; solicited AEs were collected if they were ongoing at Day 7 (post vaccination); any flares of a secondary autoimmune disease, serious AEs, medically attended AEs, new onset chronic medical conditions, and COVID-19 infections were collected from Day 1 through the end of the participant's study participation. All AEs were classified by system organ class (SOC) and preferred term, according to a standardized thesaurus (Medical Dictionary for Regulatory Activities \[MedDRA\] version 24.0. Related AEs were defined as "possibly related" (the AE has a reasonable possibility to be related; there is evidence to suggest a causal relationship) or "related" (the adverse event is clearly related). Severity was assessed according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) 5.0.
Time frame: Up to Week 48 post study vaccination
Percent of Stage 1 Adult Participants Who Experience Any Serious Adverse Events (SAEs)
An event is considered "serious" if, in the view of either the investigator or Sponsor, it results in any of the following: 1. Death. 2. Life-threatening event: considered "life-threatening" if, in the view of either the investigator or Sponsor, its occurrence places the participant at immediate risk of death. It does not include an AE that, had it occurred in a more severe form, might have caused death. 3. Inpatient hospitalization or prolongation of existing hospitalization. 4. Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. 5. Congenital anomaly or birth defect. 6. Important medical events that may not result in death, be life threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: Up to Week 48 post study vaccination
Percent of Stage 2 Adult Participants Who Experience Any Serious Adverse Events (SAEs)
An event is considered "serious" if, in the view of either the investigator or Sponsor, it results in any of the following: 1. Death. 2. Life-threatening event: considered "life-threatening" if, in the view of either the investigator or Sponsor, its occurrence places the participant at immediate risk of death. It does not include an AE that, had it occurred in a more severe form, might have caused death. 3. Inpatient hospitalization or prolongation of existing hospitalization. 4. Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. 5. Congenital anomaly or birth defect. 6. Important medical events that may not result in death, be life threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: Up to Week 48 post study vaccination
Percent of Stage 1 Adult Participants Who Experience Any Medically Attended Adverse Events (MAAEs)
Medically attended adverse event (MAAE) is defined as a hospitalization, emergency room visit, or an otherwise unscheduled visit to or from medical personnel for any reason that is considered possibly related or related to study vaccine.
Time frame: Up to Week 48 post study vaccination
Percent of Stage 2 Adult Participants Who Experience Any Medically Attended Adverse Events (MAAEs)
Medically attended adverse event (MAAE) is defined as a hospitalization, emergency room visit, or an otherwise unscheduled visit to or from medical personnel for any reason that is considered possibly related or related to study vaccine.
Time frame: Up to Week 48 post study vaccination
Percent of Stage 1 Adult Participants Who Experience Any New Onset Chronic Medical Conditions (NOCMCs)
A new onset chronic medical condition (NOCMC) is defined as any new ICD diagnosis (per current International Statistical Classification of Diseases and Related Health Problems) that is applied to the study participant during the course of the study, after receipt of the vaccine, that is expected to continue for at least 3 months and requires continued health care intervention.
Time frame: Up to Week 48 post study vaccination
Percent of Stage 2 Adult Participants Who Experience Any New Onset Chronic Medical Conditions (NOCMCs)
A new onset chronic medical condition (NOCMC) is defined as any new ICD diagnosis (per current International Statistical Classification of Diseases and Related Health Problems) that is applied to the study participant during the course of the study, after receipt of the vaccine, that is expected to continue for at least 3 months and requires continued health care intervention.
Time frame: Up to Week 48 post study vaccination
Percent of Stage 1 Adult Participants Who Experience Any Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection
Efficacy measure.
Time frame: Up to Week 48 post study vaccination
Percent of Stage 2 Adult Participants Who Experience Any Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection
COVID-19 infections (all grades) were confirmed by molecular COVID-19 testing. AEs were classified by system organ class and preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA) version 24.0.
Time frame: Up to Week 48 post study vaccination
Percentage of Stage 2 Pediatric Participants Who Seroconverted
Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center Meso Scale Discovery 3 plex assay. For concentrations below the lower limit of detection (LLOD), numeric values equivalent to LLOD/2 were assigned; concentrations above the upper limit of quantification were reported without adjustments. Antibody results collected after a documented COVID-19 infection, monoclonal antibody use, or a COVID-19 vaccine given off-study were excluded from the analyses. Participants with missing antibody data were considered missing-completely-at-random. Seroconversion was assessed in the subgroup of participants who were anti-COVID-19 antibody negative at Week 0; defined as a result less than or equal to the positive threshold value (spike=10.8424, RBD=14.0858), defined independently for spike and RBD. Seroconversion was defined as having a result greater than the positive threshold at the Week 4 visit.
Time frame: Week 4 Status Post Receipt of COVID-19 Vaccination
Fold Increase in Stage 2 Pediatric Anti-COVID-19 Antibody Levels
Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center Meso Scale Discovery 3 plex assay. For concentrations below the lower limit of detection (LLOD), numeric values equivalent to LLOD/2 were assigned; concentrations above the upper limit of quantification were reported without adjustments. Antibody results collected after a documented COVID-19 infection, monoclonal antibody use, or a COVID-19 vaccine given off-study were excluded from the analyses. Participants with missing antibody data were considered missing-completely-at-random. Fold increase was assessed in the subgroup of participants who were anti-COVID-19 antibody positive at Week 0; defined as having a result greater than the positive threshold value (spike=10.8424, RBD=14.0858), defined independently for spike and RBD. Fold increase = (antibody response at Week 4)/(antibody response at Week 0).
Time frame: Week 4 Status Post Receipt of COVID-19 Vaccination
Change in Stage 2 Pediatric Anti-COVID-19 Antibody Response
Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center (NIAID-VRC) Meso Scale Discovery (MSD) 3 plex assay (Wu-1 full-length spike, receptor binding domain (RBD), and N proteins). Wu-1 full-length spike and RBD were used to assess vaccine response. For concentrations below the lower limit of detection (LLOD), numeric values equivalent to LLOD/2 were assigned; concentrations above the upper limit of quantification were reported without adjustments. Antibody results collected after a documented COVID-19 infection, monoclonal antibody use, or a COVID-19 vaccine given off-study were excluded from the analyses. Participants with missing anti-COVID-19 antibody response data were considered to be missing-completely-at-random.
Time frame: Week 0 and Weeks 4 and 12 Status Post Receipt of COVID-19 Vaccination
Fold Inhibition of ACE2 Binding to SARS-CoV-2 Variant Antigens by Stage 2 Pediatric Samples
Antibody response was measured using the National Institute of Allergy and Infectious Disease Vaccine Research Center (NIAID-VRC) Meso Scale Discovery (MSD) V-Plex ACE2 neutralization assay which measure antibodies that block the binding of angiotensin-converting enzyme 2 (ACE2) to the SARS-CoV-2 Spike antigens, including variants of the SARS-CoV-2 virus according to the manufacturer's instruction (MSD Catalog # K15654U). Antibody results collected after a documented COVID-19 infection, monoclonal antibody use, or a COVID-19 vaccine given off-study were excluded from the analyses. Participants with missing anti-COVID-19 antibody response data were considered to be missing-completely-at-random. Results are reported as fold inhibition by a sample relative to signal from a 'diluent only' control (maximum ACE2 binding to antigen). Highly neutralizing samples show high fold inhibition whereas negative or low samples show low fold inhibition of ACE2 binding.
Time frame: Week 0 and Weeks 4 and 12 Status Post Receipt of COVID-19 Vaccination
Change in Stage 2 Pediatric Disease Activity After Receipt of Additional Doses of COVID-19 Vaccine as Measured by the Clinical Global Impression of Change (CGI-C)
The Clinical Global Impression of Change (CGI-C) is the clinician's global impression of a participant's clinical condition in terms of change relative to the start of treatment. Change is rated on a 7-point scale from 1 (very much improved) to 7 (very much worse). Higher score = more affected.
Time frame: Weeks 4 Status Post Receipt of COVID-19 Vaccine Dose
Change in Pediatric Stage 2 Disease Activity After Receipt of Additional Doses of COVID-19 Vaccine as Measured by the Physician's Global Assessment
The Physician's Global Assessment of the participant's current disease activity is assessed on a 10 cm linear horizontal visual analog scale, where the left hand extreme of the line is considered "Very Good" (0 cm, no disease activity) and the right hand extreme is considered "Very Bad" (10 cm, severe disease activity).
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Disease Activity in Stage 2 Pediatric Participants With Systemic Lupus Erythematosus (SLE) as Measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K
The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K is a validated, physician-based assessment tool used to measure the extent of lupus disease activity within the past 28 days. SLEDAI-2K total score is a weighted sum of the presence of 24 lupus disease symptoms and ranges from 0 to 105, with higher scores indicating more lupus disease activity present.
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Pediatric Stage 2 Disease Activity as Measured by the Patient Global Assessment
The Patient Global Assessment of the participant's current disease activity is assessed on a 10 cm linear horizontal visual analog scale, where the left hand extreme of the line is considered "Very Good" (0 cm, no disease activity) and the right hand extreme is considered "Very Bad" (10 cm, severe disease activity).
Time frame: Baseline and Weeks 4, 12 Post Receipt of COVID-19 Vaccine Dose
Change in Stage 2 Pediatric Disease Activity as Measured by the Patient Global Impression of Change (PGI-C)
The Patient Global Impression of Change (PGI-C) is the participant's global impression of their clinical condition in terms of change relative to the start of treatment. Change is rated on a 7-point scale from 1 (very much improved) to 7 (very much worse). Higher score = more affected.
Time frame: Weeks 4 Status Post Receipt of COVID-19 Vaccine Dose
Percent of Stage 2 Pediatric Participants Who Experience Any Grade 1 or Higher Adverse Events Related to Study Vaccine
All unsolicited adverse events (AEs) (all grades) were collected from Day 1 through Day 28; solicited AEs were collected if they were ongoing at Day 7 (post vaccination); any flares of a secondary autoimmune disease, serious AEs, medically attended AEs, new onset chronic medical conditions, and COVID-19 infections were collected from Day 1 through the end of the participant's study participation. All AEs were classified by system organ class (SOC) and preferred term, according to a standardized thesaurus (Medical Dictionary for Regulatory Activities \[MedDRA\] version 24.0. Related AEs were defined as "possibly related" (the AE has a reasonable possibility to be related; there is evidence to suggest a causal relationship) or "related" (the adverse event is clearly related). Severity was assessed according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) 5.0.
Time frame: Up to Week 48 post study vaccination
Percent of Stage 2 Pediatric Participants Who Experience Any Serious Adverse Events (SAEs)
An event is considered "serious" if, in the view of either the investigator or Sponsor, it results in any of the following: 1. Death. 2. Life-threatening event: considered "life-threatening" if, in the view of either the investigator or Sponsor, its occurrence places the participant at immediate risk of death. It does not include an AE that, had it occurred in a more severe form, might have caused death. 3. Inpatient hospitalization or prolongation of existing hospitalization. 4. Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. 5. Congenital anomaly or birth defect. 6. Important medical events that may not result in death, be life threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: Up to Week 48 post study vaccination
Percent of Stage 2 Pediatric Participants Who Experience Any Medically Attended Adverse Events (MAAEs)
Medically attended adverse event (MAAE) is defined as a hospitalization, emergency room visit, or an otherwise unscheduled visit to or from medical personnel for any reason that is considered possibly related or related to study vaccine.
Time frame: Up to Week 48 post study vaccination
Percent of Stage 2 Pediatric Participants Who Experience Any New Onset Chronic Medical Conditions (NOCMCs)
A new onset chronic medical condition (NOCMC) is defined as any new ICD diagnosis (per current International Statistical Classification of Diseases and Related Health Problems) that is applied to the study participant during the course of the study, after receipt of the vaccine, that is expected to continue for at least 3 months and requires continued health care intervention.
Time frame: Up to Week 48 post study vaccination
Percent of Stage 2 Pediatric Participants Who Experience Any Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection
COVID-19 infections (all grades) were confirmed by molecular COVID-19 testing. AEs were classified by system organ class and preferred term according to the Medical Dictionary for Regulatory Activities (MedDRA) version 24.0.
Time frame: Up to Week 48 post study vaccination